In the present study we attempted a comprehensive characterization of modulation of noradrenaline release from chick sympathetic neurons. To this purpose sympathetic neurons derived from chick lumbosacral paravertebral ganglia and kept in culture for 7 days were loaded with 0.05 mumol/l [3H]-noradrenaline and subjected to electrical field stimulation (36 pulses/3 Hz). Since the released transmitter was partially recaptured, superfusion was usually performed in the presence of (+)-oxaprotiline, an inhibitor of noradrenaline re-uptake. [3H]-Noradrenaline was released in a manner which was dependent on extracellular Ca2+ and sensitive to tetrodotoxin (TTX). omega-Conotoxin (omega-CTX; 100 nmol/l) abolished [3H]-noradrenaline release indicating that influx through omega-CTX-sensitive Ca(2+)-channels was essential for transmitter release. 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2- (trifluoromethyl)-phenyl]-3-pyridine carboxylic acid methyl ester ((+/-) Bay K 8644) and 4-(4-benzofurazanyl)-1,4-dihydro-2,6- dimethyl-3-nitro-5-pyridinecarboxylic acid isopropyl ester ((+)-202-791), agonists at L-type voltage sensitive Ca(2+)-channels (VSCCs), increased noradrenaline release and induced, in addition, an overflow of tritium which was Ca(2+)-dependent and prevented by the presence of TTX. The L-type VSCC antagonists (-)-202-791 and (+)-4-(4-benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5- pyridinedicar boxylic acid methyl, isopropyl ester) ((+)-PN 200-110) diminished [3H]-noradrenaline release. These data suggest that L-type VSCCs, probably located on the cell body of the neuron, play an additional role in modulation of release.(ABSTRACT TRUNCATED AT 250 WORDS)